For the last decade, the encapsulation and controlled release of hydrophobic species has attracted considerable interest due to the increasing number of industrial applications using hydrophobic/lipophilic active molecules. For example, in the pharmaceutical and agricultural industries, many drugs or biocides possess hydrophobic properties. Nevertheless, the means to encapsulate and controllably release these active molecules remain a challenge for these industries. On the other hand, in food, cosmetics and personal care, encapsulation and controlled release of volatile organic compounds such as flavours and perfumes, or reactive compounds such as bleaches, is becoming a dominant trend for product improvement.
Compared with traditional organic materials, inorganic matrices and more specifically ceramics have many intrinsic advantages. In particular, they are biologically inert, intrinsically hydrophilic, and represent higher mechanical strength and thermal stability. This has prompted some research in this emerging area. However, it is important to note that few of the novel inorganic delivery systems have achieved precise controlled release of the encapsulated molecules.
Such a controlled release technology has been described in “Controlled release ceramic particles, compositions thereof, processes of preparation and methods of use”, Barbe, C. J. A. and Bartlett, J., WO 01/62232 (2001). A disadvantage with the technology described by Barbe, et al. is that it only encompasses the incorporation of hydrophilic species. Hydrophobic molecules are excluded because silica formation occurs inside the hydrophilic ‘droplets’ of a water-in-oil emulsion (see FIG. 1). Hydrophobic molecules added to such a reaction mixture will be located in the external oil phase (nonpolar solvent) and thus will not be incorporated inside the silica particle as they are formed.
Modifications to the process of WO 01/62232 have been investigated in order to enable incorporation of hydrophobic species. One approach is to add a suitable surfactant into the water-in-oil droplet, which enables dispersion of hydrophobic molecules inside the hydrophilic phase. This is commonly referred to as a multiple emulsion, or double emulsion in this case—specifically an oil/water/oil emulsion. Attempts to apply this approach have been described in a co-pending patent application entitled “Particles Having Hydrophobic Materials Therein” (Kong, Barbe and Finnie)—Australian Provisional Application No. 2005903193.
An alternative approach is to reverse the emulsion and instead use an oil-in-water emulsion (see FIG. 2), which would mean that a hydrophobic species should be able to be contained inside the oil droplets. This would have a considerable advantage industrially because the main solvent is water, which may have important cost and environmental (waste management) advantages. The main challenge using this approach is to design a flexible process that allows a good control over the particle morphology (i.e. size and microstructure) to ensure a high hydrophobic payload as well as a good control over the release of this payload.
Two groups have attempted the encapsulation of actives materials inside silica particles using an oil in water emulsion approach.
Maitra et al, J. Colloid Interface Sci. 252, 82-88, (2002) have produced shell structures synthesised by precipitating a silica shell at the surface of ionic micelles. The resulting capsules are loaded by post impregnation with tetraphenyl porphyrin. 60% of the porphyrin was leached from the particles after four hours. This rapid release of the payload is due to the use of an impregnation strategy (i.e. the capsule is formed first and impregnated with the active afterwards) rather than a true encapsulation (i.e. the matrix is formed around the active). In addition, the presence of surfactant composing the micelle forming the core of the capsule helps to solubilize the hydrophobic active and consequently speeds up its release. Furthermore from an application point of view, capsules are fragile and known to rupture easily leading to uncontrolled burst release.
Prasad et al, J. Am. Chem. Soc., 125, 7860-7865 (2003) and published US patent application No. 2004/0180096 entitled “Ceramic based nanoparticles for entrapping therapeutic agents for photodynamic therapy and method of treating same” describe the production of organosilica nanoparticles having an encapsulated photosensitive drug for use in photodynamic therapy. The particles disclosed by Prasad et al are derived from stable micro-emulsions and consequently are in the nanometer range (<100 nm). Although very small particles are of interest for certain applications including drug delivery, their small size usually limits their loading and thus their usefulness. More importantly, Prasad et al disclose that the particles minimise leaching of the drug compound from within the particle such that no significant release of the drug compound takes place. Furthermore the process described by Prasad et al requires the dissolution of the hydrophobic active inside a solvent such as DMF or DMSO, which becomes co-incorporated in the particles. These solvents are known to be very toxic and thus pose significant health and environment problems when released with the actives.
There is therefore a need for a simple and versatile process for incorporating a dopant, such as a hydrophobic material, into solid or gel particles without the need to use toxic solvents. The solid or gel particles having the dopant, e.g. hydrophobic material, therein preferably would be capable of releasing the dopant, e.g. hydrophobic material, under appropriate conditions, and may be capable of doing so at a controllable rate.